Rapid translation of synaptically localized mRNAs enables a neuron to selectively modify subsets of its synapses in response to synaptic stimulation. This phenomenon is believed to contribute to the synapse-specificity of protein synthesis-dependent plasticity processes in vivo. In neurons, synapse-localized mRNAs are assembled into large cytoplasmic RNPs and transported to sites of translation. Following synaptic stimulation, specific RNAs are released from repression, polyadenylated, and translated. New data suggests that mechanisms of mRNA regulation in Drosophila neuronal granules and yeast cytoplasmic processing bodies ("P-bodies") share a highly conserved translational repression machinery (Barbee et al., submitted to Cell). Moreover, recent work in yeast suggests that mRNAs are targeted for translational repression in P bodies, in part, via a general mechanism that is mediated by the Dhh1p (yeast Me31B) and Pat1p (yeast CG5208) pathways [Coller and Parker, 2005]. To identify and further characterize functions for Me31B/Dhh1p and CG5208/Pat1p, the specific aims are to: 1. Identify functions for CG5208, a conserved RNA storage granule component, in Drosophila neurons. 2. ldentify mechanisms by which Me31B and CG5208 regulate synaptic plasticity, FMRP function, and mRNA translation in Drosophila neurons. [unreadable] [unreadable]